Combination of 5-azacitidine and Lenalidomide in Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML) Myelodysplastic Syndromes
Information source: Technische Universität Dresden
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Myelodysplastic Syndromes; Acute Myelogenous Leukemia
Intervention: Azacitidine (Drug); Lenalidomide (Drug)
Phase: Phase 1
Status: Terminated
Sponsored by: Technische Universität Dresden Official(s) and/or principal investigator(s): Uwe Platzbecker, MD, Principal Investigator, Affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus
Summary
The hypothesis of this study is that 5-aza and lenalidomide act synergistically in MDS and
AML patients with chromosomal abnormalities involving monosomy 5 or del5q. Therefore, this
phase I study will investigate the maximum tolerated dose (MTD) of lenalidomide in
combination with a fixed dose of 5-aza in this patient population.
Clinical Details
Official title: A Phase I Study of a Combination of 5-azacitidine Followed by Lenalidomide in High-risk MDS or Relapsed/Refractory AML Patients With Cytogenetic Abnormalities Including -5 or Del(5q)
Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Maximum tolerated dose (MTD) of Revlimid® (lenalidomide)in combination with Vidaza®(5-azacitidine)
Secondary outcome: Clinical and cytogenetic responseSafety (type, frequency, severity, and relationship of adverse events to study treatment)
Detailed description:
Cytogenetics are the main predictors of outcome in patients with AML. In fact, a monosomy 5
or del (5q) as single aberration are poor prognostic markers. Overall, the complete response
rate for conventionally treated patients with newly-diagnosed AML with chromosome 5
abnormalities is about 31% to 37 % and all patients rapidly relapse if not rescued by
allogeneic HSCT. The situation is almost similar in patients with high-risk MDS. Vidaza® has
been shown in clinical trials to achieve remission rates in about 29% (CR+PR) of the
patients while a total of 49% achieve improvement of blood counts. Revlimid® is also able to
achieve complete remissions in advanced MDS and even overt leukemia with or without
chromosome 5 abnormalities. Nevertheless, response rates are lower compared to low-risk MDS
(IPSS Low/INT-1). Therefore, Revlimid® seems to be too weak as a single agent, but a
promising compound for a combination therapy.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Understand and voluntarily sign an informed consent form.
- Age >=18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Relapsed or refractory AML (>30% blasts, FAB classification)with karyotype
abnormalities involving monosomy 5 or del(5q) or MDS and t-MDS INT-2 or HIGH
according to IPSS classification with karyotype abnormalities involving monosomy 5 or
del(5q) either previously treated or untreated
- Not eligible for an immediate allogeneic HSCT (due to donor unavailability)
- All previous MDS or AML specific therapy with exception of corticosteroids not
exceeding doses of 10mg/day prednisone must have been discontinued at least 1 week
prior to study enrollment.
- Non-hematological toxicity (except alopecia) resulting from previous treatment must
be resolved to WHO CTC Grade ≤ 2.
- ECOG performance status of < 3 at study entry.
- Laboratory test results within these ranges: Serum creatinine <= 2. 0 mg/dL, Total
bilirubin <= 3 x ULN, AST (SGOT) and ALT (SGPT) <= 3 x ULN
- Females of childbearing potential must agree to use a reliable form of contraception
or to practice complete abstinence from heterosexual intercourse during the following
time periods related to this study: 1) for at least 28 days before starting study
drug; 2) while participating in the study; and 3) for at least 28 days after
discontinuation from the study.
Exclusion Criteria:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed
while on study).
- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.
- Known hypersensitivity to thalidomide, lenalidomide, 5-azacitidine or mannitol.
- Myocardial infarction within 6 months before study entry, New York Heart Association
Class III or IV heart failure, uncontrolled angina or severe uncontrolled ventricular
arrhythmias.
- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.
- Uncontrolled lung disease.
- Known positive for HIV or acute infectious hepatitis, type A, B or C.
- Participation in another clinical study in the 4 weeks prior to enrollment or during
this study.
Locations and Contacts
Medizinische Klinik und Poliklinik I, Uniklinik, Dresden, Germany
Universitätsklinikum Düsseldorf, Klinik für Hämatologie/Onkologie/klinische Immunologie, Düsseldorf 40225, Germany
Klinikum der J.W. Goethe-Universität, Medizinische Klink II, Frankfurt 60590, Germany
Technische Universität München, Klinikum Rechts der Isar, München 81675, Germany
Additional Information
Starting date: June 2009
Last updated: December 17, 2013
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